12-63150508-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000706.5(AVPR1A):​c.329G>A​(p.Cys110Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AVPR1A
NM_000706.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66
Variant links:
Genes affected
AVPR1A (HGNC:895): (arginine vasopressin receptor 1A) The protein encoded by this gene acts as receptor for arginine vasopressin. This receptor belongs to the subfamily of G-protein coupled receptors which includes AVPR1B, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor mediates cell contraction and proliferation, platelet aggregation, release of coagulation factor and glycogenolysis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AVPR1ANM_000706.5 linkc.329G>A p.Cys110Tyr missense_variant Exon 1 of 2 ENST00000299178.4 NP_000697.1 P37288X5D2B0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AVPR1AENST00000299178.4 linkc.329G>A p.Cys110Tyr missense_variant Exon 1 of 2 1 NM_000706.5 ENSP00000299178.3 P37288

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152242
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460928
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
726846
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.329G>A (p.C110Y) alteration is located in exon 1 (coding exon 1) of the AVPR1A gene. This alteration results from a G to A substitution at nucleotide position 329, causing the cysteine (C) at amino acid position 110 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Benign
-0.064
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Benign
0.15
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.15
T
Polyphen
0.56
P
Vest4
0.70
MutPred
0.41
Gain of catalytic residue at V105 (P = 0.0046);
MVP
0.68
MPC
1.5
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.68
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs976163430; hg19: chr12-63544288; API